JP7274478B2 - 置換された-3H-イミダゾ[4,5-c]ピリジン及び1H-ピロロ[2,3-c]ピリジンシリーズの新規なエクトヌクレオチドピロホスファターゼ/ホスホジエステラーゼ-1(ENPP1)並びにがん免疫治療薬としてのインターフェロン遺伝子(STING)モジュレータのための刺激剤 - Google Patents
置換された-3H-イミダゾ[4,5-c]ピリジン及び1H-ピロロ[2,3-c]ピリジンシリーズの新規なエクトヌクレオチドピロホスファターゼ/ホスホジエステラーゼ-1(ENPP1)並びにがん免疫治療薬としてのインターフェロン遺伝子(STING)モジュレータのための刺激剤 Download PDFInfo
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- JP7274478B2 JP7274478B2 JP2020527860A JP2020527860A JP7274478B2 JP 7274478 B2 JP7274478 B2 JP 7274478B2 JP 2020527860 A JP2020527860 A JP 2020527860A JP 2020527860 A JP2020527860 A JP 2020527860A JP 7274478 B2 JP7274478 B2 JP 7274478B2
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- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
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| JP2021533110A (ja) * | 2018-08-01 | 2021-12-02 | スティングレイ・セラピューティクス・インコーポレイテッド | 癌免疫療法剤としての新規エクトヌクレオチドピロホスファターゼ/ホスホジエステラーゼ−1(ENPP1)の置換3H−イミダゾ[4,5−c]ピリジンおよび1H−ピロロ[2,3−c]ピリジンシリーズならびにインターフェロン遺伝子刺激因子(STING)調節剤 |
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| EP3807264A1 (en) | 2018-06-12 | 2021-04-21 | Ryvu Therapeutics S.A. | Modulators of stimulator of interferon genes (sting) |
| MA54879A (fr) * | 2019-02-01 | 2021-12-08 | Univ Leland Stanford Junior | Inhibiteurs d'enpp1 et méthodes de modulation de réponse immunitaire |
| CN113795267A (zh) | 2019-03-12 | 2021-12-14 | 艾库斯生物科学有限公司 | 致癌基因驱动的癌症的治疗 |
| BR112021018947A2 (pt) | 2019-03-28 | 2022-02-08 | Lupin Ltd | Compostos macrocíclicos como agonistas de sting |
| CN113874397A (zh) | 2019-03-29 | 2021-12-31 | 艾库斯生物科学有限公司 | 利用鉴定的腺苷指纹治疗癌症 |
| AU2020291796B2 (en) | 2019-06-12 | 2024-01-18 | Ryvu Therapeutics S.A. | Next-generation modulators of stimulator of interferon genes (STING) |
| GEP20247627B (en) | 2019-07-22 | 2024-05-27 | Lupin Ltd | Macrocyclic compounds as sting agonists and methods and uses thereof |
| US20230002387A1 (en) | 2019-09-16 | 2023-01-05 | Aten Porus Lifesciences Pvt. Ltd. | 2-amino-s6-substituted thiopurine compounds as inhibitors of the enpp1 protein |
| KR102915463B1 (ko) * | 2019-12-11 | 2026-01-19 | 리부 세라퓨틱스 에스.에이. | 인터페론 유전자 자극제(sting)의 조절제인 헤테로사이클릭 화합물 |
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| US20230159469A1 (en) | 2020-05-08 | 2023-05-25 | Txinno Bioscience Inc. | Novel phthalazine derivative having ectonucloeotide pyrophosphatase/phosphodieste rase inhibitory activity, and use thereof |
| KR102682428B1 (ko) | 2020-05-08 | 2024-07-05 | 주식회사 티씨노바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제-포스포디에스터라아제의 저해 활성을 갖는 신규한 프탈라진 유도체 및 이들의 용도 |
| KR102720206B1 (ko) | 2020-12-29 | 2024-10-21 | 주식회사 티씨노바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제-포스포디에스터라아제의 저해 활성을 갖는 신규한 나프티리딘온 유도체 및 이들의 용도 |
| WO2022146022A1 (ko) | 2020-12-29 | 2022-07-07 | 주식회사 티씨노바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제-포스포디에스터라아제의 저해 활성을 갖는 신규한 나프티리딘온 유도체 및 이들의 용도 |
| KR102686866B1 (ko) | 2021-01-29 | 2024-07-19 | 주식회사 티씨노바이오사이언스 | 엑토뉴클레오티드 피로포스파타아제-포스포디에스터라아제의 저해 활성을 갖는 신규한 벤조트리아졸 유도체 및 이들의 용도 |
| US20240116882A1 (en) | 2021-01-29 | 2024-04-11 | Txinno Bioscience Inc. | Novel benzotriazole derivative having inhibitory activity against ectonucleotide pyrophosphatase-phosphodiesterase, and use thereof |
| AU2023213905A1 (en) * | 2022-01-28 | 2024-07-11 | Insilico Medicine Ip Limited | Ectonucleotide pyrophosphatase-phosphodiesterase 1 (enpp1) inhibitors and uses thereof |
| US20230346771A1 (en) | 2022-04-29 | 2023-11-02 | Petragen, Inc. | Inhibitors of enpp1 and modulation of bone growth |
| WO2026006739A1 (en) * | 2024-06-28 | 2026-01-02 | Riboscience Llc | Bicyclic heteroaryl derivatives as ectonucleotide pyrophosphatase phosphodiesterase 1 inhibitors for the treatment of certain diseases |
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| EP1020451B1 (en) | 1997-03-25 | 2005-06-15 | Kowa Co., Ltd. | Anilide compounds and drugs containing the same |
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| Title |
|---|
| Czarnocka-Janowicz, Anna; Sawlewicz, Jozef; Jakubowski, Joachim; Janowiec, Mieczyslaw,Synthesis and tuberculostatic activity of some derivatives of 2-mercaptoimidazo[4,5-c]pyridine,Acta Poloniae Pharmaceutica ,1979年,36(5),,529-37 |
| Database REGISTRY,2010年,Retrieved from STN international [online] ;retrieved on 1 July 2022,RN 903165-95-7 他 |
| LEI CHANG,IMIDAZOPYRIDINE- AND PURINE-THIOACETAMIDE DERIVATIVES: POTENT INHIBITORS OF NUCLEOTIDE PYROPHOSPHATASE/PHOSPHODIESTERASE 1 (NPP1),JOURNAL OF MEDICINAL CHMISTRY,2014年,VOL:57,PAGE(S):10080-10100,https://pubs.acs.org/doi/abs/10.1021/jm501434y |
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|---|---|---|---|---|
| JP2021533110A (ja) * | 2018-08-01 | 2021-12-02 | スティングレイ・セラピューティクス・インコーポレイテッド | 癌免疫療法剤としての新規エクトヌクレオチドピロホスファターゼ/ホスホジエステラーゼ−1(ENPP1)の置換3H−イミダゾ[4,5−c]ピリジンおよび1H−ピロロ[2,3−c]ピリジンシリーズならびにインターフェロン遺伝子刺激因子(STING)調節剤 |
| JP7461927B2 (ja) | 2018-08-01 | 2024-04-04 | スティングレイ・セラピューティクス・インコーポレイテッド | 癌免疫療法剤としての新規エクトヌクレオチドピロホスファターゼ/ホスホジエステラーゼ-1(ENPP1)の置換3H-イミダゾ[4,5-c]ピリジンおよび1H-ピロロ[2,3-c]ピリジンシリーズならびにインターフェロン遺伝子刺激因子(STING)調節剤 |
Also Published As
| Publication number | Publication date |
|---|---|
| EP3658138B1 (en) | 2023-04-19 |
| WO2019023635A8 (en) | 2020-02-20 |
| CN111615388B (zh) | 2023-11-14 |
| WO2019023635A1 (en) | 2019-01-31 |
| EP3658138A4 (en) | 2021-03-31 |
| US10689376B2 (en) | 2020-06-23 |
| CN111615388A (zh) | 2020-09-01 |
| EP3658138A1 (en) | 2020-06-03 |
| JP2020532578A (ja) | 2020-11-12 |
| US20190031655A1 (en) | 2019-01-31 |
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